U.S. and European Regulators Accept Applications for AbbVie's Venetoclax, the First Potential BCL-2 Inhibitor for Chronic Lymphocytic Leukemia

· Priority Review granted by the U.S. Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) in adults who have received at least one prior therapy, including patients with 17p deletion

· Marketing Authorization Application (MAA) validated by European Medicines Agency (EMA) for treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion or TP53 mutation

Jan 12, 2016, 08:30 ET from AbbVie

NORTH CHICAGO, Ill., Jan. 12, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) accepted AbbVie's New Drug Application (NDA) granting priority review for venetoclax for the treatment of chronic lymphocytic leukemia (CLL) in adults who have received at least one prior therapy, including patients with 17p deletion. With priority review, the FDA's goals include a faster timeline for review of six months, compared to 10 months for the standard review period. Additionally, AbbVie announced the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for venetoclax for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion or TP53 mutation.

Venetoclax is an inhibitor of the B-cell lymphoma-2 (BCL-2) protein being developed in partnership with Genentech and Roche to treat CLL. Venetoclax is believed to lead some cells, including some cells with CLL, to undergo apoptosis, or cell death.

The FDA granted venetoclax Breakthrough Therapy Designation (BTD) in April 2015 for the treatment of CLL in previously treated patients with the 17p deletion genetic mutation, underscoring the potential for venetoclax to provide substantial improvement over current therapies in this difficult to treat patient population.

"The FDA acceptance and EMA validation of AbbVie's Venetoclax submissions mark a major step forward as we work to become a global leader in oncology, providing new therapies for patients with cancer," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "Patients are always our number one priority and we accelerated our efforts to bring venetoclax, the first BCL-2 inhibitor, to patients with CLL in need of new therapies, including those with 17p deletion who typically have a poor prognosis."

The NDA and MAA are supported by pivotal data from a Phase 2, open-label study of venetoclax in patients with relapsed/refractory CLL with 17p deletion, a genetic variation in CLL associated with a poor patient prognosis. In August 2015, AbbVie announced the Phase 2 study met its primary endpoint of achieving an overall response rate, according to an assessment by an independent review committee. The safety profile was similar to other venetoclax studies and no unexpected safety signals were reported. 

About Venetoclax
Venetoclax is an investigational oral B-cell lymphoma-2 (BCL-2) inhibitor being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be over expressed in some cancer types. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax is being developed in collaboration with Genentech and Roche. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other cancers. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority. According to the FDA, BTD is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for BTD includes preliminary clinical evidence, demonstrating a drug may have substantial improvement on at least one clinically significant endpoint compared to available therapies.

About Chronic Lymphocytic Leukemia (CLL), 17p Deletion and TP53 Mutation
CLL is a slow-progressing cancer of the bone marrow and blood in which the bone marrow makes too many lymphocytes, a type of white blood cell.1 It is the most common leukemia diagnosed in adults in western countries.2

The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent.Approximately 3-10 percent of CLL patients are found to have the 17p deletion mutation at diagnosis, and it occurs in 30-50 percent of patients with relapsed/refractory CLL.4 The median life expectancy for CLL patients with 17p deletion is less than 2-3 years.5 Chromosome 17 contains the TP53 gene6, which is involved in regulating the division and death of normal cells.7 Deletion of 17p or mutations in TP53 are associated with rapid disease progression and short survival.8

About the Phase 2 Study
The Phase 2, multicenter, international, open label clinical trial was designed to evaluate the efficacy and safety of venetoclax monotherapy in CLL patients with 17p deletion who relapsed or who were refractory to existing therapies. The study enrolled 158 patients, 107 in the main study cohort evaluating efficacy, and 50 patients in the safety expansion cohort. 

The primary efficacy endpoint was overall response rate and the safety evaluations were the number and percentage of patients who experienced treatment-related adverse events, changes in physical exam findings, including vital signs, changes in clinical laboratory test results and changes in cardiac assessment findings. Secondary efficacy outcome measures included complete remission rate, partial remission rate, duration of response, overall survival and progression-free survival, among others.

About AbbVie Oncology 
AbbVie's oncology research is focused on the discovery and development of targeted therapies that work against the processes cancers need to survive. By investing in new technologies and approaches, AbbVie is breaking ground in some of the most widespread and difficult-to-treat cancers, including glioblastoma multiforme, multiple myeloma and chronic lymphocytic leukemia. AbbVie's oncology pipeline includes multiple new molecules in clinical trials being studied in more than 15 different cancers and tumor types. For more information on AbbVie Oncology, please visit http://oncology.abbvie.com. 

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements 
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

1 American Cancer Society (2013) "Leukemia – Chronic Lymphocytic."http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf.
2Eichhorst, B. et al. "Chronic Lymphocytic Leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up." Annals of Oncology 22 (Supplement 6): vi50-vi54, 2011.
3 Sellner, L. et al. (2013) "What Do We Do with Chronic Lymphocytic Leukemia with 17p Deletion?" Curr Hemetol Malig Rep. 8(1):81-90.
4 Schnaiter, A. et al. (2013) "17p Deletion in Chronic Lymphocytic Leukemia: Risk Stratification and Therapeutic Approach."  Hematol Oncol Clin N Am 27 (2013) 289–301. 
5 Stilgenbaur, S, and Zenz, T, (2010) "Understanding and Managing Ultra High-Risk Chronic Lymphocytic Leukemia." ASH Education Book. 2010(1):481-488.
6 Schnaiter, A. et al. (2013) "17p Deletion in Chronic Lymphocytic Leukemia: Risk Stratification and Therapeutic Approach."  Hematol Oncol Clin N Am 27 (2013) 289–301.
7 Hallek, M. et al.  (2015) "Chronic Lymphocytic leukemia: 2015 Update on Diagnosis, Risk Stratification, and Treatment.
8 Schnaiter, A. et al. (2013) "17p Deletion in Chronic Lymphocytic Leukemia: Risk Stratification and Therapeutic Approach."  Hematol Oncol Clin N Am 27 (2013) 289–301.

 

SOURCE AbbVie



RELATED LINKS

http://www.abbvie.com